Wegner Group: Computational Physiology

Our group is interested in functional neuroimaging techniques. These techniques provide quantitative insights into ongoing brain activity and its relation to brain health. The main technique we are investigating is electroencephalography (EEG), but also magnetic resonance imaging (MRI) and related imaging methods. We are interested in combining and developing new methodological approaches to quantify biological signals, including information theory and machine learning. Applications include wake-sleep transitions, epilepsy, and dementia.

Current projects:

EEG quantification of brain state transitions in health and neurological disease (wake-sleep, anaesthesia, epilepsy, dementia)
Complexity and syntax analysis of EEG microstate sequences
Electrical source imaging in epilepsy
Quantitative EEG analysis in Parkinson Disease

The TNF Team

A vibrant group of research scientists with expertise in Neuroscience, Cell and Molecular Biology, Gene therapy, Neuroimmunology, Neurophysiology and CNS disorders

Impact and Applications

Clinical trials:
- BaDGE^® cochlear implant neurotrophin gene therapy [Phase I/II non-randomized, controlled trial, evaluating the safety and efficacy of neurotrophin gene therapy delivered during cochlear implant surgery; ACTRN12618001556235; (www.cingt.info)]
  - BaDGE™
- Noise adaptation: a biomarker for hearing loss vulnerability (supporting establishment of a first-in-class prognostic hearing test)
Translational stroke & traumatic brain injury (TBI) small molecule therapeutics
Targeted DNA / RNA therapeutics: Epilepsy, white-matter disorders, eye disease, immunotherapies, hearing and bionics
Pain neuro-immunology
Learning and addiction neural circuits

Industry Partners & Cross-Institutional Research Agreements

Bionics Inst. U. Melbourne
Boehringer-Ingelheim Germany
CNRS & Descartes U. Paris, France
Cochlear Ltd Australia
Hertie Institute for Clinical Brain Research, University of Tuebingen, Germany
Interacoustics, Copenhagen
Macquarie University Hearing Hub, Sydney
Mission Massimo Foundation
Murdochs Children’s Research Institute, Melb.
National Institute of Physiological Sciences (NIPS), Okazaki, Japan
NextSense Australia
Nyrada Inc. Australia
Passe & Williams Memorial Foundation
Shanghai Inst. Neuroscience, China
Shinshu University, Matsumoto, Japan
Touchlight Genetics UK
U. Auckland, N.Z.
U. Calif. San Diego, USA
U. Miami, Florida, USA
University of Queensland
University of Sydney
Walter Reed Army Institute of Research (WRAIR) Brain Trauma Neuroprotection Branch, MD, USA

TNF Patents:

BaDGE^® non-viral gene delivery: [link to BaDGE precision naked DNA/mRNA therapeutics below p.17]

US Patent US9533138B2
US Patent US11013917B2
US Patent US20180169399A1
US20220054827A1 pending
PCT WO2021072507A1 pending
AU Patent. Application No. 2022903976

Neuroprotection:

US 2017/0202932 A1
AU2013286815

Hearing loss:

WO2019169440

Pinyon et.al, Adv. Science Paper [Back cover].

Pending Pinyon Jonquieres end of November [MD to add the DOI Then link to the paper]

Elena Venuti ‘A mouse model of HBSL disease enabling AAV gene therapy delivered in utero’ won best student poster prize 2024 Australian Gene and Cell Therapy Society (AGCTS) Meeting – 30^th Oct to 1^st Nov; [Pls create link to file, MD to supply file to upload]

Connor Karozis presented ‘A precision gene delivery platform targeting peripheral nerve injury’ Australian Gene and Cell Therapy Society (AGCTS) Meeting – 30^th Oct to 1^st Nov.
Fusing biology with the bionic ear | Engineering and Technology Magazine. Heidi Vella 07/07/23 - reports the CINGT clinical trial in the context of innovations in medical bionics

Channel 9 News June 17th 2022 – CINGT clinical trial patient experience https://www.facebook.com/watch/?v=3341989752711664

Channel 9 News Aug 2024, 40 years of cochlear implants in Australia
https://www.facebook.com/share/v/iSB3yWMPhC2ueoXo/?mibextid=oFDknk
2024-2025 – Australia’s Economic Accelerator Seed grant “Establishing Vision-BaDGE anti-VEGF DNA therapy for age-related macular degeneration. Australian Government Department of Education AEA Seed Tranche 1. G. von Jonquieres, G. Housley, N. Lovell, M. Kalloniatis, E. Crawford, A. Al Abed, J. Cederholm, D. Froehlich, M. Duxbury, I. Goon, L. Pearson.

2022 - 2025 - National Health & Medical Research Council (NHMRC - Australia) IDEAS Grant “Bionic-array Directed Gene Electrotransfer for Treating Focal Brain Disorders”. CIs: Gary Housley, Nigel Lovell, Matthias Klugmann, Holger Lerche, Thomas Wuttke, Frederic von Wegner, Amr Al Abed, Georg von Jonquieres, Jennie Cederholm; AIs: Jeremy Pinyon, Caroline Rae, Dominik Froehlich, Andre Bongers, Daniel Scherman, Junichi Nabekura.

2021 - ongoing – Industry Contract – Boehringer Ingelheim – Brain-BaDGE® for DNA & RNA therapeutics targeting epilepsy enabling grant – Research Beyond Borders

2020 – ongoing: Industry Contract - Nyrada Pty Ltd to support Traumatic Brain Injury collaborative research including the Walter Reed Army Institute for Research (WRAIR).

2020 – 2025: National Health & Medical Research Council (NHMRC - Australia) IDEAS Grant “Cochlear purinergic adaptation as a biomarker for vulnerability to noise-induced hearing loss. CIs: Gary Housley, Xue Liu, Shin-ichi Usami, Zhiyong Liu, Allen Ryan, Catherine McMahon, David McAlpine, Jennie Cederholm, Peter Thorne, Srdjan Vlajkovic, AIs: David Ryugo, Frederic von Wegner.

2019 - 2024 – The Garnett Passe and Rodney Williams Memorial Foundation conjoint grant “Progression of hearing performance following cochlear implant neurotrophin gene augmentation. CIs: G Housley, C Birman, W Lai, J Pinyon, D McAlpine.

2025-2026 – ANZCA Project Grant – “Investigating the Effects of Spinal Direct Current Stimulation on Glial Cells for Chronic Pain Neuromodulation.” Mohabbati Vahid, Moalem-Taylor Gila, Aplin Felix, Papan Mohammadkazem.

2023-2025 – MS Australia – “Nanoconjugates for treating neuropathic pain in experimental autoimmune encephalomyelitis, an animal model of MS.” CIs: Moalem-Taylor Gila, Mao Guangzhao, Pascal Carrive; AIs: Housley, Potas, Krishnan.

2022-2025 – NSW Schizophrenia Research Grants Program – “Unlocking midbrain microglia as treatment targets for dopamine dysregulation in schizophrenia.” Tertia Purves-Tyson, Jennifer Cornish, Gila Moalem-Taylor, Melissa Bauman.

2022-2023 (Extended to 2024) – UNSW Medicine Neuroscience, Mental Health and Addictions Theme and SPHERE Clinical Academic Group Seed Grant – “Nanoconjugates for treating neuropathic pain in an animal model of multiple sclerosis.” CIs: Moalem-Taylor Gila, Mao Guangzhao, Pascal Carrive; AIs: Housley, Krishnan.
Gene Electrotransfer via Conductivity-Clamped Electric Field Focusing Pivots Sensori-Motor DNA Therapeutics: “A Spoonful of Sugar Helps the Medicine Go Down” Advanced Science 30/2024. Jeremy L. Pinyon, Georg von Jonquieres, Edward N. Crawford, Amr Al Abed, John M. Power, Matthias Klugmann, Cherylea J. Browne, David M. Housley, Andrew K. Wise, James B. Fallon, Robert K. Shepherd, John Y. Lin, Catherine McMahon, David McAlpine, Catherine S. Birman, Waikong Lai, Ya Lang Enke, Paul M. Carter, James F. Patrick, Robert D. Gay, Corinne Marie, Daniel Scherman, Nigel H. Lovell, Gary D. Housley
https://doi.org/10.1002/advs.202401392

[MD to put details of paper and image] Pending Pinyon Jonquieres end of November [Then link to the paper]

Parmar J; von Jonquieres G; Gorlamandala N; Chung B; Craig AJ; Pinyon JL; Birnbaumer L; Klugmann M; Moorhouse AJ; Power JM; Housley GD, 2024, 'TRPC Channels Activated by G Protein-Coupled Receptors Drive Ca2+ Dysregulation Leading to Secondary Brain Injury in the Mouse Model', Translational Stroke Research, 15, pp. 844 - 858, http://dx.doi.org/10.1007/s12975-023-01173-1

Cederholm JME; Parley KE; Perera CJ; von Jonquieres G; Pinyon JL; Julien JP; Ryugo DK; Ryan AF; Housley GD, 2022, 'Noise-induced hearing loss vulnerability in type III intermediate filament peripherin gene knockout mice', Frontiers in Neurology, 13, http://dx.doi.org/10.3389/fneur.2022.962227

Close-field electroporation gene delivery using the cochlear implant electrode array enhances the bionic ear. Jeremy L. Pinyon, Sherif F. Tadros, Kristina E. Froud, Ann C. Y. Wong, Isabella T. Tompson, Edward N. Crawford, Myungseo Ko, Renée Morris, Matthias Klugmann, Gary D. Housley. Science Translational Medicine 23 Apr 2014 (Cover). Vol. 6, Issue 233, pp. 233ra54

DOI: 10.1126/scitranslmed.300817

[Image to hyperlink to paper: https://www.science.org/doi/abs/10.1126/scitranslmed.3008177

Fröhlich D; Kalotay E; von Jonquieres G; Bongers A; Lee B; Suchowerska AK; Housley GD; Klugmann M, 2022, 'Dual-function AAV gene therapy reverses late-stage Canavan disease pathology in mice', Frontiers in Molecular Neuroscience, 15, http://dx.doi.org/10.3389/fnmol.2022.1061257

Housley GD, Morton-Jones R., Vlajkovic SM, Telang RS, Paramananthasivam V, Tadros SF, Wong ACY, Froud KE, Cederholm JME, Sivakumaran Y, Snguanwongchai P, Khakh BS, Cockayne DA, Thorne PR., Ryan AF (2013). ‘ATP-gated ion channels mediate adaptation to elevated sound levels’ Proceedings of the National Academy of Sciences of the U.S.A.110, 18:7494-7499. doi: 10.1073/pnas.1222295110

Yan D, Zhu Y, Walsh T, Xie D, Yuan H, Sirmaci A, Fukikawa T, Wong ACY, Loh TL, Du L, Grati M, Vlajkovic SM, Blanton S, Ryan AF, Chen Z-Y, Thorne PR, Kachar B, Tekin M, Zhao H-B, Housley GD, King M-C, Liu X-Z (2013) ‘Mutation of the ATP-gated P2X2 receptor leads to progressive hearing loss and increased susceptibility to noise’, Proc Natl Acad Sci USA. 110,6:2228-2233. doi: 10.1073/pnas.1222285110. Epub 2013 Jan 23

Scientific Blog – Naked Scientist interview “How can we improve cochlear implants” 29/04/2014. http://www.thenakedscientists.com/forum/index.php?topic=51272.msg434877#msg434877

http://nakeddiscovery.com/downloads/split_individual/14.04.29/Naked_Scientists_Show_14.04.29_1002233.mp3

Froud KE, Wong ACY, Cederholm JME, Klugmann M, Sandow SL, Julien J-P, Ryan AF, Housley GD (2015) Type II spiral ganglion afferent neurons drive medial olivocochlear reflex suppression of the cochlear amplifier. Nature Communications 10.1038/ncomms8115 (May 12th, 2015).

This publication received a commentary in Nature and Gary Housley was interviewed by Naked Scientists

Link: http://www.natureasia.com/en/research/highlight/9898

Link: The Naked Scientists Science Interview:

May 18th, 2015. “Selective Hearing” www.thenakedscientists.com/HTML/specials/show/20150518-4/